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F l u i d Th e r a p y

Options and Rational Selection

Christopher G. Byers, DVM, CVJ

KEYWORDS
 Endothelial glycocalyx  Hypovolemia  Dehydration  Crystalloid  Colloid
 End points of resuscitation

KEY POINTS
 The discovery of endothelial glycocalyx has dramatically changed the understanding of
vascular permeability, and should be considered when developing fluid therapy plans.
 Dehydration and hypovolemia are terms to describe fluid derangements, and each must
be addressed uniquely to maximally benefit patients.
 Synthetic colloids have many potential benefits but appropriate patient selection is vital for
maximizing patient safety while using them.

INTRODUCTION

Total body water (TBW) comprises 60% of body weight.1 The 2 main fluid compart-
ments in the body are the intracellular fluid (ICF) and extracellular fluid (ECF). The ICF
compartment comprises approximately 60% of TBW, and the ECF compartment
makes up the other 40%.1 ICF is found inside the bilayered cell plasma membrane,
and is in osmotic equilibrium with the ECF. The ECF is divided into 3 components:
the interstitial compartment, the intravascular compartment, and the third space.1
The interstitial compartment is the fluid space that surrounds cells and allows move-
ment of ions, proteins, and nutrients across cell membranes. Approximately 75% of
ECF is located in the interstitial compartment and is continuously turned over and recol-
lected by the lymphatic vessels. The intravascular compartment comprises approxi-
mately 25% of the ECF, and fluids do not normally accumulate in the third space.1

TRADITIONAL STARLING FORCES

Movement of fluid across capillary walls is essential for maintaining a continuous ex-
change of oxygen and carbon dioxide between the body’s cells and the blood supply.
There is a continual exchange between fluid compartments in the body, which

Disclosure: The author has nothing to disclose.
VCA Midwest Veterinary Referral and Emergency Center, 9706 Mockingbird Drive, Omaha, NE
68127, USA
E-mail address: christopherbyers@me.com

Vet Clin Small Anim - (2016) -–-
http://dx.doi.org/10.1016/j.cvsm.2016.09.007 vetsmall.theclinics.com
0195-5616/16/ª 2016 Elsevier Inc. All rights reserved.
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provides nourishment to cells and removes waste products. Hydrostatic pressure and
oncotic pressure work against each other to produce this fluid movement. Hydrostatic
pressure is the pressure exerted by any fluid in a confined space. If fluid is in a
container, there will be some pressure applied to the wall of that container. Picture
a column-shaped container. The pressure pushing against its wall is greater at the bot-
tom than at the top partly because of the force of gravity. Capillaries are the equivalent
of a column-shaped container turned on its side. As fluid moves through a capillary,
hydrostatic pressure causes fluid to move into the interstitial compartment. This
movement also means that the hydrostatic pressure decreases as the blood moves
from the arteriolar to the venous end of the capillary. The fluid pushed out through
the capillary wall by hydrostatic pressure is called filtrate.
Blood contains plasma proteins that displace some water in blood, and less water in
the intravascular compartment creates a concentration gradient between the intravas-
cular and interstitial spaces. The osmotic pressure generated by plasma proteins is
called oncotic pressure or colloid osmotic pressure (COP). Plasma proteins pull water
into the intravascular compartment, whereas the force of osmosis equalizes the
amount of water in the intravascular compartments and the interstitial fluid.

ENDOTHELIAL GLYCOCALYX

According to traditional Starling forces described earlier, hydrostatic pressure pushes
water out of capillaries and oncotic pressure pulls fluid into the intravascular compart-
ment.2 Since Dr Starling originally published his hypothesis, further research regarding
fluid dynamics has emerged. It is now known that the luminal surface of endothelial
cells is lined with a glycocalyx of membrane-bound macromolecules composed of
sulfated proteoglycans, hyaluronan, glycoproteins, and plasma proteins; the endothe-
lial glycocalyx (EG).
The high rate of resorption of interstitial fluid in the venular segments of the micro-
circulation hypothesized by Dr Starling does not happen. Filtration across the vascular
barrier is largely independent of the bulk colloid concentration surrounding the vessel.
In regions with high intravascular pressure, the inwardly directed oncotic pressure
gradient across the EG prevents flooding of the interstitial space in conjunction with
the high resistance to flow within the narrow strand gaps of the endothelium.3 Within
low-pressure sections, free and easy access of plasma constituents toward the tissue
cells allows a highly effective exchange of nutrients and waste products. Therefore,
the fluid shift is modest if the endothelial surface layer is intact because of the low hy-
drostatic and oncotic pressure gradients in these segments.3
The principal role of the EG is to maintain the vascular permeability barrier.3 Other
meaningful functions include shielding vascular walls from direct exposure to blood
flow and mediating shear stress–dependent nitric oxide (NO) production.3 The EG
also promotes retention of vascular protective enzymes and helps preserve the intra-
vascular concentration of coagulation inhibition factors.3 The EG also helps modulate
the inflammatory response by preventing leukocyte adhesion and binding of chemo-
kines, cytokines, and growth factors to the endothelium.3

TISSUE SAFETY FACTORS

Extracellular edema forms when excess fluid accumulates in the interstitial compart-
ment; this accumulation occurs as a result of either abnormal leakage from the intra-
vascular compartment to the interstitial compartment or a failure of the lymphatics to
return fluid from the interstitium to the intravascular compartment, or both. Altered
capillary filtration occurs because of an increased capillary filtration coefficient,
Fluid Therapy 3

increased capillary hydrostatic pressure, decreased capillary oncotic pressure, or
some combination of these. Inadequate lymphatic return of fluid to the intravascular
compartment occurs secondary to neoplasia, various infections, postoperative com-
plications, or congenital or developmental abnormalities.
The body has several mechanisms to help prevent the formation of extracellular
edema.4 The interstitial compartment does not accommodate a large volume of fluid,
and thus the interstitial hydrostatic pressure increases rapidly to prevent extravasa-
tion.5 Increased movement of fluid from the intravascular compartment to the intersti-
tium also decreases the interstitial oncotic pressure. Combined with increased lymph
flow, albumin is washed out of the interstitium to decrease interstitial oncotic pres-
sure.6 Increased interstitial pressure then drives augmented lymph flow that helps
remove the fluid.7

CRYSTALLOIDS

Crystalloids contain variable amounts of electrolytes, water, and dextrose, and may be
characterized by tonicity and their effect on acid-base status. Crystalloids are used
either to replace sodium loss or maintain the status quo. Replacement fluids contain
sodium at concentrations similar to normal plasma (approximately 140 mmol/L),
whereas maintenance fluids have sodium concentrations similar to normal total
body concentration (70 mmol/L). Replacement crystalloids and maintenance crystal-
loids may also be classified as isotonic or hypotonic, respectively. Approximately one-
third of administered isotonic replacement fluid remains in the intravascular space and
two-thirds enters the interstitial space.
Common examples of replacement fluids are lactated Ringer solution (LRS),
Plasma-Lyte, Normosol-R, and 0.9% sodium chloride. The first 3 have potassium con-
centrations similar to plasma and contain a lactate, acetate, or gluconate buffer,
respectively, to maintain a physiologic pH. Animals normally lose potassium through
urine, and this loss is augmented during aldosterone release and sodium conserva-
tion. Accordingly, replacement fluids should be supplemented with potassium when
used long term. Normal saline contains no potassium or buffers, and is the fluid of
choice for hypercalcemia given that it contains no calcium. Normal saline may exac-
erbate volume overload, metabolic acidosis, heart disease, and hypertension.
Maintenance fluids are simply designed to replace daily sodium losses, and are
appropriate for long-term administration. Dextrose is commonly supplemented to
approximate plasma tonicity and prevent hemolysis. These lower-sodium fluids do
not stay in the intravascular space, do not meaningfully expand blood volume, and
should not be used for volume resuscitation.
Hypertonic saline may be used for rapid intravascular volume expansion, because it
pulls fluid primarily from the interstitial compartment. Volume expansion is short lived,
because the sodium redistributes throughout the extracellular compartment quickly.
Hypertonic saline is available as both 7% to 7.5% and 23% solutions; the 23% solu-
tion must be diluted before administration. Do not administer hypertonic saline faster
than 1 mL/kg/min to avoid vagally mediated bradycardia and potential cardiopulmo-
nary arrest.

COLLOIDS

Colloids are large molecules that remain in the intravascular space because of the
Gibbs-Donnan equilibrium. Smaller volumes compared with crystalloids are required
to achieve intravascular expansion. When used appropriately, these fluids are less likely
to induce hemodilution, hypoproteinemia, extracellular edema, and fluid overload.8
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Synthetic colloids, most notably dextrans and hydroxyethyl starches (HESs),
contain high-molecular-weight particles that allow these fluids to increase COP.
Because albumin is the main contributor to COP, colloids are advantageous in the
treatment of hypoalbuminemia because of their ability to increase COP. The HESs
most commonly used in veterinary medicine are hetastarch, pentastarch, and tetra-
starch. The differences among hetastarch, pentastarch, and tetrastarch are the
average molecular weight of the particles and the degree of substitution of glucose
units on the starch particle with a hydroxyethyl group.
Several features are used to describe unique qualities of HES solutions:
1. Concentration: concentration mainly influences the initial volume effect. A common
concentration, 6%, is iso-oncotic in vivo, and thus 1 L replaces 1 L of blood loss.
Concentrations range from 6% to 10%.
2. Mean molecular weight: hetastarch has an average molecular weight of 450 kDa,
pentastarch of 260 kDa, and tetrastarch of 130 kDa. Larger molecules are
degraded more slowly, and, accordingly, solutions with a higher average molecular
weight last longer.
3. Molar substitution: molar substitution refers to the modification of the original sub-
stance by the addition of hydroxyethyl groups. The higher the degree of molar sub-
stitution, the greater the resistance to degradation; consequently, the fluid remains
in the intravascular space longer. A value of 0.7 indicates the HES preparation has
an average of 7 hydroxyethyl residues per 10 glucose subunits. Starches with this
level of substitution are called hetastarches, and similar names are applied to
describe other levels of substitution (0.4, tetrastarch; 0.5, pentastarch; 0.6,
hexastarch).
4. C2:C6 ratio: the C2:C6 ratio refers to the site where substitution occurs on the initial
glucose molecule. The higher the C2:C6 ratio, the longer is the T1/2 (half-life) and sub-
sequently the longer the persistence in blood. Synthetic colloids have been associated
with adverse effects, including affecting coagulation and increasing the potential for
volume overload because of the efficacy of expanding intravascular volume.
Natural colloids are available for infusion. Fresh frozen plasma (FFP) is collected and
spun within 6 hours and frozen, ideally at 70 C, for up to 1 year. This fluid contains
stable clotting factors (II, VII, IX, X), labile clotting factors (V, VIII), von Willebrand factor,
fibrinogen, and albumin; it does not contain red blood cells and platelets. Indications
for FFP administration are replacement of all clotting factors, anticoagulant rodenti-
cide intoxication, von Willebrand disease, and hemophilia (A and B). A common
dose for replacement of clotting factors in 10 to 20 mL/kg. Frozen plasma (FP) is
collected similarly to FFP, but is stored for longer than 1 year. It contains stable clotting
factors, fibrinogen, and albumin, but does not contain red blood cells, platelets, and
labile clotting factors. Fresh plasma may be used for hemophilia B, and is adminis-
tered at similar doses to FFP. Because of the potential for hypervolemia, use of FFP
and FP to treat hypoalbuminemia is not practical or safe, except in very small patients.
Hemoglobin-based oxygen carriers (HBOC; eg, Oxyglobin) are ultrapurified, poly-
merized, stroma-free bovine hemoglobin products that promote oxygen off-loading
at the tissue level and are potent colloids. The hemoglobin is suspended in a modified
LRS solution, has an osmolality of 300 mOsm/kg, and has a 3-year shelf life. Admin-
istration of HBOCs does not require blood typing or crossmatching. The potential
beneficial effects of HBOCs stem from their COP and vasoconstrictive properties.
They are efficient scavengers of NO and thus can help combat severe vasodilatation,
which is commonly observed in patients with systemic inflammatory response syn-
drome (SIRS), severe sepsis, and septic shock.9,10 These fluids are bovine products,
Fluid Therapy 5

so 1-time use is recommended because of the potential for antibody formation and
subsequent immunologic reactions. The HBOCs cause the patient’s mucous mem-
branes, sclera, and urine to turn red or yellow, and affect colorimetric diagnostic blood
and urine tests. The availability of HBOCs is currently extremely limited because of
decreased commercial production.
With progressive hypoalbuminemia, COP decreases, which allows fluid to shift from
the intravascular space into the interstitial space and potentially cause edema if tissue
safety factors are overwhelmed. Serum albumin has been used in critically ill patients
to help support blood pressure and to aid in the treatment of significant hypoalbumi-
nemia. At present, 2 types of serum albumin are available for administration: human
serum albumin (HSA) and canine serum albumin (CSA). HSA has been used success-
fully in both dogs and cats, but both acute and delayed immunologic reactions have
been documented.11,12 This product is available as a solution, and may be infused
in 4-hour aliquots over 4 to 72 hours. CSA is available as a lyophilized powder for
reconstitution with sterile saline. Concentrations currently range from 4% to 25%
and do not contain any preservatives. Thus CSA must be administered within 6 hours.
Infused albumin remains in the intravascular space for 24 hours, and close monitoring
for fluid overload is recommended. The reported doses for both HSA and CSA range
from 100 mg/kg to 6.3 g/kg.

HYPOVOLEMIA VERSUS DEHYDRATION

The pathophysiology of dehydration and volume depletion must be understood if
these conditions are to be properly recognized and appropriately treated. Indiscrimi-
nate use of these terms risks confusion and therapeutic errors. Hydration status is a
measure of interstitial fluid content, and is determined by evaluating skin turgor, mois-
ture of the mucous membranes, and possibly enophthalmos. Volume status is a mea-
sure of tissue perfusion, and is initially evaluated by checking heart rate, capillary refill
time, mucous membrane color, and blood pressure.
Hypovolemic animals commonly have prolonged capillary refill times, tend to have
pale mucous membranes, and are often hypotensive. Hypovolemic dogs often pre-
sent with tachycardia, but most cats either have normal heart rates or sinus brady-
cardia. If hypovolemia is severe, obtundation, weak peripheral pulses, lack of
venous distension when the veins are occluded, or some combination of these may
be documented. Hypovolemia may exist concurrently with dehydration. Nevertheless,
clinicians must replace circulating volume before rehydrating. Treatment of hypovole-
mia should be finished within 1 to 2 hours, and often requires rapid intravenous admin-
istration of replacement crystalloids, known as shock boluses (40–50 mL/kg for cats;
90 mL/kg for dogs). Typically, one-quarter of the total shock volume should be admin-
istered, and then end points of resuscitation (EOR) reassessed to determine whether
more volume is necessary.

ROUTE OF ADMINISTRATION

Common routes of fluid administration in dogs and cats include intravenous (periph-
eral, central, or peripherally inserted central catheters), subcutaneous, enteral, intra-
osseous, and intraperitoneal. For patients with hypovolemia, an intravenous
catheter with short length and large bore diameter is recommended. If venous access
is not immediately possible, the intraosseous route may be used until vascular access
is achieved. The subcutaneous route is not appropriate for hypovolemic patients
because peripheral vasoconstriction severely limits absorption. With mild dehydra-
tion, the subcutaneous route may suffice. Dextrose should not be delivered
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subcutaneously, and potassium delivered via this route may cause discomfort. Sub-
cutaneous fluids are frequently administered at 10 to 20 mL/kg per site. Enteral water
supplementation is commonly used in the intensive care unit.

VOLUME AND RATE OF ADMINISTRATION

When determining the appropriate fluid volume and rate of administration, the
following questions should be asked:
 Is the patient hypovolemic?
 Is the patient dehydrated?
 What are the patient’s daily physiologic requirements?
 Are there any ongoing losses? If yes, how much?
By answering these questions, the clinician is addressing the 3 major components
of fluid administration: resuscitation, replacement, and maintenance. During fluid
resuscitation, intravascular volume is restored with intravenous fluid administration.
Hypovolemic patients require fluid resuscitation, and the volume infused depends
on the stage of shock (Table 1).
Stabilizing interventions for patients with shock should target EOR, particularly:
 Restoration of normal vital signs
 Normalization of abnormal mentation
 Restoration of normal blood pressure (systolic >80–90 mm Hg)
 Normal serum lactate concentration (<2.5 mmol/L)
 Central venous oxygen saturation (ScvO2) greater than 70%
 Packed cell volume (PCV) greater than 25%
 Urine output (UOP) greater than 1 mL/kg/h
 Pulse oximetry greater than 93% at a fraction of inspired oxygen of 21%
 Central venous pressure (CVP) of 5 to 10 cm H2o
Initially, for hypovolemia, an isotonic crystalloid should be administered at a shock
rate (dogs, 20 mL/kg, up to 90 mL/kg; cats, 10 mL/kg, up to 40–50 mL/kg) over 15 mi-
nutes, and then EOR should be reassessed.13 With hypoproteinemic hypovolemia,
administration of a synthetic colloid may be appropriate; these fluids should be deliv-
ered over 20 to 30 minutes (dogs, 5 mL/kg, up to 20 mL/kg; cats, 2–5 mL/kg, up to
10 mL/kg) and EOR should be reassessed after each bolus.13
After effectively addressing hypovolemia, an appropriate fluid therapy plan must
address dehydration, daily physiologic requirements, and ongoing losses. Isotonic
crystalloids should be used for fluid replacement (correcting dehydration and replen-
ishing ongoing losses). Clinical signs of dehydration include tacky mucous mem-
branes, decreased skin turgor, enophthalmia, and prolonged capillary refill time.
The volume required to correct dehydration is the product of the estimated percentage
of dehydration and body weight in kilograms, and should be delivered over

Table 1
Clinical signs associated with stages of shock

Compensatory Normal vital signs (or mild tachycardia), injected mucous
membranes, rapid CRT, normal blood pressure
Early decompensatory Tachycardia (dogs), pale mucous membranes, prolonged CRT,
decreased mentation, hypothermia, hypotension
Late decompensatory Bradycardia, severe hypotension, absent CRT, weak or absent
peripheral pulses, hypothermia, obtundation, oliguria, or anuria
Fluid Therapy 7

approximately 4 to 24 hours depending on the patient’s risk for hypervolemia. After
correcting dehydration, the patient’s fluid therapy plan should be reevaluated.
Ongoing losses may be estimated by weighing diarrhea and vomitus, and frequent
body weight monitoring is recommended to help gauge the patient’s fluid status.
Daily physiologic requirements, also termed maintenance requirements (not to be
confused with maintenance crystalloids), are most commonly calculated in clinical
practice with one of the following formulas:

(30  BW in kilograms) 1 70 5 mL/d (for patients between 2–50 kg)

80  BW0.75 5 mL/d

where BW is body weight. Both isotonic and hypotonic crystalloids may be appro-
priate and the ultimate choice of crystalloid type should be determined based on
the patient’s volume status and serum electrolyte concentrations. Fluids should al-
ways be titrated to effect. Fluid therapy is commonly used during the perianesthetic
period. Potential benefits of providing fluids to healthy patients during the perianes-
thetic period include cardiovascular support, the ability to counter potential
anesthesia-induced adverse reactions (eg,: vasodilatation), and the correction of
normal ongoing losses.

HYPOTENSIVE RESUSCITATION

Hypotensive resuscitation is a method of fluid resuscitation that has been advocated
for stabilization of patients with uncontrolled hemorrhage and surgery planned to
attain hemorrhage control. Two types of hypotensive resuscitation have been
described: limited volume resuscitation (also known as permissive hypotension) and
delayed resuscitation. To perform limited volume resuscitation, conservative volumes
of intravenous fluids are administered before achieving definitive control of hemor-
rhage. The fluids improve but do not normalize blood pressure and tissue perfusion.
This form of therapy targets a specific preoperative blood pressure range, commonly
a mean arterial pressure of 40 to 60 mm Hg. Patients who receive delayed resuscita-
tion receive no volume resuscitation until definitive control of hemorrhage has been
attained. Fluid resuscitation targeting appropriate EOR is instituted only after hemor-
rhage has been controlled.
The value of hypotensive resuscitation in veterinary patients is controversial.14–17
The timing of resuscitation and reestablishment of hemostasis is seemingly critical
because most studies documenting successful use of this technique had short pre-
operative times. Most veterinary patients with trauma with intra-abdominal hemor-
rhage spontaneously achieve hemostasis, do not require surgical intervention, and
should not receive hypotensive fluid resuscitation. Patients with nontraumatic hemor-
rhage commonly have preoperative wait times longer than those in published studies,
and therefore hypotensive resuscitation results in protracted hypotension and con-
tributes to the development of SIRS and multiple organ dysfunction syndrome.
Although hypotensive resuscitation may be beneficial for some patients, the benefits
must be carefully weighed against the potential risks of prolonged hypotension in
each patient.

EARLY GOAL-DIRECTED THERAPY

The profound inflammation associated with SIRS and sepsis induces vascular leakage
secondary to endothelial dysfunction. Subsequently, fluid extravasation results in
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relative and absolute hypovolemia, hypoperfusion, and possibly septic shock. Fluid
therapy is the mainstay of resuscitation of patients with SIRS, sepsis, severe sepsis,
and septic shock. In 2001 the concept of early goal-directed therapy (EGDT) was intro-
duced, which is a specific algorithm for managing patients presenting with septic
shock.18 Aggressive fluid resuscitation to achieve specific end points was recommen-
ded. In-hospital mortality was 30.5% in the EGDT group and 46.5% in the standard
therapy group, a finding that was statistically significant.18 Patients in the EGDT group
also had significantly higher mean ScvO2, lower lactate concentration, lower base
deficit, and higher pH than patients assigned to standard therapy.18 Subsequently,
clinical guidelines, the Surviving Sepsis Campaign (SSC) guidelines, for the manage-
ment of human patients with severe sepsis and septic shock were developed and are
routinely updated.19,20
Aggressive initial fluid resuscitation is considered the cornerstone of initial therapy
for human and veterinary patients with severe sepsis and septic shock. The SSC
guidelines recommend immediately instituting volume resuscitation in affected people
according to a specific protocol. Within 3 hours of presentation, clinicians should:
 Measure lactate concentration
 Obtain blood cultures before administration of antibiotics
 Administer broad-spectrum antibiotics
 Administer a crystalloid (30 mL/kg) for hypotension or hyperlactatemia
(4.0 mmol/L)
If patients have persistent hypotension (MAP <65 mm Hg) after initial fluid resusci-
tation or if they had an initial lactate concentration greater than or equal to 4.0 mmol/L,
further assessment is warranted. Clinicians may either repeat a focused examination
or evaluate 2 of the following:
 CVP
 ScvO2
 Dynamic assessment of fluid responsiveness (ie, passive leg raise test)
 Bedside cardiovascular ultrasonography
Vasopressors should be used within 6 hours for those patients with persistent hypo-
tension despite aggressive initial fluid resuscitation. Transfusion with packed red
blood cells to maintain PCV greater than 30% and vasopressor therapy may also
be helpful. Serial monitoring of perfusion parameters, particularly lactate, should be
pursued, and lactate concentrations should be normalized as rapidly as possible.
To date, the optimal composition and volume of resuscitation fluid are not known in
human or veterinary patients. Since the EGDT study, subsequent investigations have
been conducted to document potential benefits. Results have been mixed depending
on the patient population studied. The Australasian Resuscitation in Sepsis Evaluation
(ARISE) study in 1600 human patients with early septic shock failed to show a reduc-
tion of all-cause mortality at 90 days despite using EGDT interventions.21 Prospective
randomized controlled trials have not been conducted in veterinary medicine. Thus,
the ideal guidelines for resuscitation of veterinary patients with SIRS, sepsis, severe
sepsis, and septic shock are similarly unknown at this time.

FLUID ADDITIVES

Potassium supplementation is regularly required for veterinary patients, particularly
those who receive large volumes of replacement fluids. Common causes of hypoka-
lemia include gastrointestinal fluid loss, diuresis, and anorexia. Administration of
Fluid Therapy 9

bicarbonate, insulin, dextrose, or some combination of these can induce a hypokale-
mic state through intracellular shifting if concurrent potassium supplementation is not
provided. Clinical signs of hypokalemia may include muscle weakness, abnormal gait,
ileus, cervical ventroflexion (particularly in cats), and dysrhythmias (atrial or ventricular
premature contractions). Electrocardiography may show a prolonged Q-T interval
(>0.25 seconds). Potassium deficits may be variable, and supplementation is patient
dependent. The rate of supplementation should generally not exceed 0.5 mEq/kg/h
without attentive patient monitoring.
Supplementation of B vitamins is common in veterinary patients, particularly in a
critical care setting. These vitamins are inactivated on exposure to ultraviolet light,
but are fairly stable for approximately 72 hours in environments with fluorescent lights
and minimal exposure to natural sunlight. All B vitamins are water soluble, and thus are
only stored in the body for a few days. They are also commonly lost in polyuric dis-
eases, and deficiency can contribute to anorexia. Thiamine deficiency has been asso-
ciated with neurologic deficits, and cobalamin deficiency is common in patients with
exocrine pancreatic insufficiency and distal small intestinal disease. Supplementation
with pure thiamine or cobalamin is recommended if deficiency in either vitamin is sus-
pected or confirmed, because vitamin B complex solutions do not contain adequate
amounts of either thiamine or cobalamin.
Magnesium has multiple important functions as a cofactor in enzymatic reactions,
contributor to the tertiary structure of proteins, and participant in cell membrane func-
tion. Hypomagnesemia is common in veterinary critical care patients, and deficiency
has been associated with prolonged hospitalization.22 Hypomagnesemia should be
suspected in patients with refractory hypokalemia. Mild hypomagnesemia is often cor-
rected by infusing magnesium-containing fluids. Marked deficiency (ionized magne-
sium concentration <0.35 mmol/L) should be addressed with a constant-rate infusion
of magnesium sulfate or chloride at an initial dosage of 0.75 to 1.0 mEq/kg/d for 24 hours
followed by a 50% dose reduction for an additional 3 to 5 days.

MONITORING

With the provision of fluid therapy comes the requirement to monitor the patient’s
response to that intervention. Multiple parameters may be readily evaluated to assess
the patient’s response to prescribed fluid therapy. Common physical variables are:
 Body weight: the change in a patient’s body weight is a noninvasive method for
evaluating fluid gain or loss on a day-to-day basis. Because several variables
predispose this measurement to errors, clinicians are encouraged to measure
patients’ body weight at the same time of day using the same scale to minimize
variability.
 Mucous membranes: dehydrated patients frequently have dry mucous mem-
branes. Thus, a change from tacky mucous membranes to moist ones commonly
indicates a positive response to fluid therapy.
 Capillary refill time (CRT): patients with poor perfusion typically have prolonged
capillary refill times, and poor perfusion frequently arises from hypovolemia. An
improving CRT suggests improved perfusion.
 Skin turgor: evaluation of the patient’s skin turgor or degree of skin tenting has
historically been used to assess various degrees of dehydration. Overhydrated
patients are commonly described as having a gelatinous feeling to their skin
and may readily develop gravity-dependent edema. Geriatric patients and under-
weight patients have decreased turgor normally and overweight or obese pa-
tients commonly have increased skin turgor. Thus, evaluation of skin turgor in
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these patients is an unreliable indicator of hydration status and response to pre-
scribed fluid therapy.
 Heart rate: compensatory and early decompensatory hypovolemic shock in dogs
and occasionally cats is associated with reflex tachycardia. Cats do not consis-
tently develop this compensatory response because of concurrent sympathetic
and vagal stimulation. Providing appropriate bolus fluid therapy to hypovolemic
dogs and cats resolves the compensatory tachycardia if present, indicating a
positive response to fluid therapy.
In addition to easily measured physical variables, trained veterinary medical
personnel may measure other values with minimal patient discomfort, particularly:
 Blood pressure: marked hypovolemia can overwhelm the patient’s homeostatic
responses to result in hypotension (MAP <60 mm Hg). Hypertension is exceed-
ingly rare in patients with fluid overload because of the large capacitance of the
venous circulation, and patients may manifest hypotension without hypovolemia
because of decreased cardiac contractility, decreased systemic vascular resis-
tance, or both.
 UOP: normal UOP is 1 to 2 mL/kg/h, and urine output of 0.5 to 1 mL/kg/h and less
than 0.3 mL/kg/h indicate oliguria and anuria, respectively.
 CVP: CVP is the pressure within the lumen of the cranial vena cava and is thought
to be equivalent to right atrial pressure. CVP is influenced by cardiac output (CO),
venous return, and venous tone, and thus this variable estimates the relationship
between blood volume and capacity. Excluding myocardial dysfunction or
increased pulmonary resistance, CVP is a reliable indicator of an effective circu-
lating blood volume. In dogs and cats, normal CVP is 0 to 10 cm H20, and mea-
surements should always be compared with previous results. Trends in CVP are
more useful than single measurements for assessing response to fluid therapy.
 Lactate: hypoperfusion secondary to a decrease in effective circulating volume
readily results in tissue hypoxia, which induces type A lactic acidosis. Improving
tissue perfusion via fluid resuscitation may resolve the type A hyperlactatemia.
However, tissue hypoxia may occur without volume depletion (eg, decreased
CO, decreased systemic vascular resistance, decreased PaO2) and type B lactic
acidosis may occur without hypoxia, and thus lactate concentrations must be in-
terpreted carefully.
Measuring the amount of fluid provided to a patient, as well as urinary and fecal
output, is essential for providing the best fluid therapy. Serially and accurately moni-
toring a patient’s ins and outs is potentially challenging, but astute clinicians must
be keenly aware of all possible sources of fluid loss from their patients, particularly los-
ses via urine, feces, vomitus, blood, and cavitary effusions.
Although healthy animals are generally tolerant of excessive fluid administration,
debilitated patients are less able to endure excessive volume. Signs of fluid overload
and overhydration include weight gain, restlessness, tachypnea, dyspnea, serous
nasal discharge, chemosis (cats), adventitious lung sounds (eg, crackles), tachy-
cardia, gallop rhythm (cats), coughing, and jugular venous distension.

CONTROVERSIES
Synthetic Colloids
Measurements of urine specific gravity should be made before administration of
certain HESs, particularly hetastarch. Hetastarch molecules less than 50 kD are freely
filtered by the glomerulus, and falsely cause high refractometer readings. Total solids
Fluid Therapy 11

(TS) measurements via refractometry are also affected, because hetastarch yields a
value of 4.5 g/dL alone and 3.0 g/dL when mixed 1:1 with a hypooncotic diluent.23
Thus, TS measurements in patients receiving a hetastarch as a constant-rate infusion
for more than 24 hours tend to trend toward a range of 3.0 to 4.5 g/dL. Thus, direct
measurement of serum albumin or COP in these patients provides a more accurate
assessment of oncotic status.
HESs have been recommended for resuscitation in patients with hypoalbuminemia
or sepsis given their ability to induce a more rapid and lasting circulatory stabilization
than crystalloids. The use of HES has been called into question and advised against in
some human patients considering various adverse reactions reported in randomized
clinical trials, most notably coagulation alterations, immunologic reactions, increased
incidence of acute kidney injury (AKI), and need for renal replacement therapy.24 An
increased incidence of adverse outcomes, including AKI and death, occurred in
dogs in the intensive care unit (ICU) that received 10% HES compared with a general
ICU population. Randomized controlled clinical trials evaluating the safety of HES in
both dogs and cats are needed, and clinicians should limit the use of HES in patients
with preexisting renal injury or those at risk for renal tubular injury.25
HESs have been implicated in inducing several coagulation abnormalities in various
patient populations, including dogs and cats. The potential to induce a coagulopathy
must be considered when contemplating the use of HES in septic patients. Both
in vitro and in vivo studies in dogs and cats have documented adverse effects on
platelet function and coagulation.26–28 However, the clinical relevance of these studies
is not known, and clinical prospective investigation is warranted. At this time, use of
HES in patients with preexisting coagulation abnormalities is cautioned.
Although immediate and delayed immunologic reactions to HES have rarely been
documented in humans, only anecdotal reports of such reactions exist in veterinary
medicine to the author’s knowledge.

Albumin
Although human and canine albumins have significant amino acid homology, some
important differences exist between the two molecules, thus raising concerns over an-
tigenicity. A recent retrospective study of 64 dogs that received HSA did not identify
any significant problems.29 Nevertheless, the current recommendation is that clini-
cians should not administer HSA again more than 1 week after the initial dosing
because of the risk of antigenicity. Both HSA and canine albumin are hyperoncotic so-
lutions, and thus fluid overload and overhydration are possible.

SUMMARY

Administration of appropriate types and volumes of parenteral fluids is of paramount
importance when treating sick and debilitated patients, especially those fighting crit-
ical illness. Fluid selection and accurate calculations must be performed logically and
accurately to maximize positive outcomes. Knowledge of fluid types, as well as the
complex relationship of the body’s fluid compartments, helps clinicians to develop
rational fluid therapy plans for their patients.

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